The contrast media used in radiological examination of medical technology include hyperosmolar ionic and hypo-osmolar nonionic contrast media, wherein hyperosmolar ionic contrast medium has the disadvantages of leading to increased intravascular fluid, angiectasis, rising pulmonary venous pressure, vascular endothelial injury and large neurotoxicity, and rendering toxic and side effects in use, whereas nonionic contrast medium, applicable for blood vessel, nervous system, contrast enhanced CT scanning and the like, has the advantages of relatively low osmosis, low viscosity, and low toxicity, etc., alleviating toxic and side effects greatly. Among others, iopromide is a novel hypo-osmolar nonionic contrast medium, which has lower osmosis than ordinary ionic contrast medium, similar osmotic pressure to that of blood plasma, modest viscosity favorable for injection and less toxicity than ionic contrast medium, and may be used in myelography, more safely.
3-methylamino-1,2-propanediol is an important material for producing iopromide as a hypo-osmolar nonionic contrast medium, and its content has a direct influence on the quality, the content of impurities, as well as the clinical effect of the final product iopromide, particularly on the occurrence of adverse reaction, etc.. If the content of impurities in 3-methylamino-1,2-propanediol is high, the synthesized iopromide in use will result in the following reactions: mild nausea, emesis, dizziness, acute emesis, chilly feeling, generalized urticaria, facial or laryngeal edema, bronchospasm, dyspnea-stethalgia, celialgia, headache or limb convulsion, etc.. In severe cases, prostration, unconsciousness, pneumonedema, heart arrest or ventricular fibrillation, acute arrhythmia or myocardial infarct, or even death may be incurred. In view of the aforementioned reasons, Schering Co. of Germany has been extremely critical of the quality of 3-methylamino-1,2-propanediol since 1985 when iopromide was officially put into market, and only a few countries can produce the product satisfying its quality demand.
The processes for preparing 3-methylamino-1,2-propanediol may be categorized on the basis of starting material into epichlorohydrin process, glycerin chlorohydrin process, glycide process and glyceraldehyde process, wherein the aminating agent includes aqueous monomethylamine solution or gaseous monomethylamine used directly; it may be categorized on the basis of operational pressure into low pressure process, high pressure process, etc.; it may be categorized on the basis of production process into batch process and continuous process. Both epichlorohydrin and glycerin chlorohydrin processes take the route involving glycerin chlorohydrin, and they only differ in cost. Glycide and glyceraldehyde processes have high production cost, poor economic benefit and low purity of product. Therefore, glycerin chlorohydrin process is the most commonly used production process at present, wherein glycerin chlorohydrin and aqueous monomethylamine solution, as the starting materials at a feeding ratio of 1:2.9-3.9 by weight, are subjected to amination reaction under a pressure of 0.3-0.4 MPa, and then an aliphatic alcohol such as methanol or ethanol is used as a solvent to dilute the viscous solution to filter out monomethylamine chloride, followed by purification by means of distillation to obtain the product 3-methylamino-1,2-propanediol. The existing production of 3-methylamino- 1,2-propanediol mainly has the following disadvantages: (1) excessive feeding ratio of monomethylamine to glycerin chlorohydrin, bringing difficulty for recovery of monomethylamine, and increasing energy consumption; (2) low purity of the product and high content of impurities; (3) low conversion of glycerin chlorohydrin; (4) the requirement of using an aliphatic alcohol such as methanol or ethanol, as a solvent, to dilute the viscous solution and to filter out monomethylamine chloride, which adds operational steps; and (5) long production cycle.